HebaBiz Biotech is pleased to announce that in November 2021, the Center for Drug Evaluation (CDE) of The National Medical Products Administration (NMPA) of China has approved the application for phase III clinical study of Clevudine (L-FMAU), a drug candidate under development for chronic hepatitis B virus (HBV), the application of which was made by HebaBiz Biotech on August 18, 2021, marking another major milestone on its achievement on advancing the clinical study for liver diseases.
L-FMAU was introduced from Yale University and HebaBiz Biotech obtained its exclusive license for anti-hepatitis B virus in Greater China. With the help of Professor Yung-Chi Cheng, Chairman of HebaBiz Biotech's Biotechnology Advisory Committee (postdoctoral supervisor at Yale University of Dr. James Zhou), Dr. Zhou, HebaBiz Biotech's founder, as one of the participants in the pharmacology research program of the world's first-in-class anti-HBV drug Lamivudine, has a deep understanding of the pharmacology and limitations of current anti-hepatitis B drugs, and are committed to developing L-FMAU as a new generation best-in-class anti-HBV new drug with potential in pursuing the aim of functional cure. HebaBiz Biotech practices the research strategy of "introduction, absorption and re-innovation" and initiative. Upon obtaining the license from Yale University, one of the world's top universities, HebaBiz Biotech continued in-depth research, focusing on the drug-feasibility and practical aspects, and has achieved new breakthroughs and progress.
HBV infection is a worldwide epidemic. According to WHO, there are about 257 million chronic HBV infected patients worldwide, and about 887,000 people die of HBV-related diseases every year. In China, 77% of patients with cirrhosis and 84% of patients with HCC were caused by HBV. It is estimated that the prevalence of HBsAg in the general population in China is 5%-6%, and there are about 70 million chronic HBV infections, of which about 20-30 million are CHB patients. At present, it is difficult for drugs on the market to achieve functional cure of hepatitis B virus. Drugs of various mechanisms are still in clinical stage to develop breakthrough therapy, but most of them are in phase I or phase II clinical stage, and none has been approved for new drug application.
L-FMAU is a synthetic β-L nucleoside analogue discovered in the laboratory of Professor Yung-Chi Cheng at Yale University. Unlike most NAs, L-FMAU is phosphorylated to Clevudine-5'-triphosphate (CLV-TP) in cells and binds to reverse transcriptase to inhibit HBV replication non-competitively. It is not incorporated into the HBV DNA chain and does not participate in mitochondrial DNA and nuclear DNA chain replication. Therefore, L-FMAU is different from other NAs in its mechanism of action, inhibiting all the processes of HBV DNA replication to form viral genome, including initiation, polymerization, elongation and so on, thus inhibiting cccDNA formation.
In addition to inhibiting virus replication and reducing cccDNA copy number, HebaBiz Biotech also discovered that L-FMAU can regulate hepatocyte immune-related genes, modify cell microenvironment, reactivate autoimmunity, and induce apoptosis in cells. Given L-FMAU's dual regulatory mechanism of antiviral and immune reactivation, HebaBiz Biotech designed the pulsed administration protocol to achieve the purpose of sustained virus suppression after drug withdrawal, and can potentially achieve functional cure for some patients.
L-FMAU has two key development values as follows: 1. It can realize long-term drug withdrawal for some patients, and solve the long-term medication compliance issues of patients and the risk of renal function damage caused by long-term use of NAs; 2. Pulsed administration can give full play to its immune reactivation advantage and further clearance capacity of cccDNA/HBsAg to a certain extent while avoiding and solving the disadvantage of long-term continuous administration of L-FMAU; It is expected to realize the potential of achieving the long-term goal of functional/clinical cure for some patients and provide patients with better treatment options.
Responding to this milestone, Dr. Zhou remarked:
"While I was studying pharmacology guided by my...
(All Rights Reserved)